Silicosis is a well-acknowledged occupational lung disease caused by inhalation of a large amount of free silica dust during the production period and eventually a considerable negative impact on the patients' quality of life. Autophagy exerts a critical influence on immune and inflammatory responses during the pathogenesis of pulmonary fibrosis. In this study, we sought to determine whether autophagy is involved in silicosis's pathogenesis and how it may affect pulmonary cellular physiology. In the animal experiments, we found persistent activation of autophagy in the development of pulmonary fibrosis, which was also accompanied by tumor necrosis factor and transforming growth factor expression increased. Therefore, the autophagy signaling pathway may regulate the inflammatory response and affect the progression of fibrosis. Further, in vitro experiments, we used LY294002, RAPA, and N-acetylcysteine (NAC) intervened autophagy. Our results showed that PI3K/Akt/mTOR signaling pathway is involved in the autophagy changed mediated by SiO₂ exposed, and autophagy might play a protective role in the progression of pulmonary fibrosis. Additionally, NAC's effect is not apparent on SiO₂-mediated autophagy through the PI3K/Akt/mTOR signaling pathway, but it can reduce the inflammatory response on NR8383 cells mediated by SiO2-exposed. Nevertheless, it's interesting that NAC can reduce the inflammatory response on NR8383 cells mediated by SiO₂-exposed. Taken together, our data demonstrated that SiO₂-exposed can induce pulmonary fibrosis along with autophagy both in vivo and in vitro, NAC could alleviate the inflammatory response NR8383 cells by SiO₂-exposed through non PI3K/Akt/mTOR signaling pathway, and the specific mechanism of its action needs further studying.

中文翻译：

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二氧化硅粉尘暴露通过自噬信号诱导肺纤维化

矽肺是一种公认​​的职业性肺部疾病，是由于在生产期间吸入大量游离二氧化硅粉尘引起的，最终对患者的生活质量产生相当大的负面影响。在肺纤维化的发病机制中，自噬对免疫和炎症反应产生重要影响。在这项研究中，我们试图确定自噬是否参与了矽肺的发病机制以及它如何影响肺细胞生理学。在动物实验中，我们发现自噬在肺纤维化的发展过程中持续激活，同时伴随着肿瘤坏死因子和转化生长因子表达的增加。因此，自噬信号通路可能调节炎症反应并影响纤维化的进展。更多，在体外实验中，我们使用 LY294002、RAPA 和 N-乙酰半胱氨酸 (NAC) 干预自噬。我们的结果表明PI3K/Akt/mTOR信号通路参与了SiO介导的自噬变化₂暴露，自噬可能在肺纤维化的进展中起保护作用。此外，NAC通过 PI3K/Akt/mTOR 信号通路对 SiO ₂介导的自噬作用不明显，但它可以减少 SiO2 暴露介导的 NR8383 细胞的炎症反应。然而，有趣的是，NAC 可以降低 NR8383 细胞由暴露于 SiO ₂介导的炎症反应。总之，我们的数据表明，SiO ₂暴露可以在体内和体外诱导肺纤维化和自噬，NAC 可以通过 SiO ₂减轻 NR8383 细胞的炎症反应-通过非PI3K/Akt/mTOR信号通路暴露，其作用的具体机制有待进一步研究。